1. Field of the Invention
The present invention is broadly concerned with a subcutaneously implantable enzymatic sensor characterized by small size, optimum geometry and linearity of sensor response over the concentration range of interest. More particularly, it is preferably concerned with an implantable glucose sensor of this type designed to provide, in conjunction with a suitable signal processing unit, a current which is proportional to subcutaneous glucose concentration. In preferred forms, glucose sensors of the invention are based on the enzyme-catalyzed oxidation of glucose to gluconic acid and hydrogen peroxide, the latter being monitored amperometrically by the sensors.
2. Description of the Prior Art
There have been a great many attempts in the past to develop viable implantable sensors for continuous in vivo measurements of biochemicals. For example, considerable effort has been made to devise reliable implantable sensors for monitoring glucose concentrations in blood. Such determinations are useful in a variety of applications, e.g., in the treatment of diabetics. One difficulty in providing a reliable implantable glucose sensor is that glucose levels in the bloodstream of a patient vary on a time basis and are normally dependent upon the physical activity of the individual, his food, beverage and sugar intake, his metabolic rate, and other individualized factors. Furthermore, the geometry of the sensor must be such as to adapt to implantation in a living patient.
Glucose sensors have been proposed in the past which rely upon the well-established enzyme-catalyzed oxidation of glucose wherein glucose and oxygen function as substrates for the enzyme glucose oxidase in the production of gluconic acid and hydrogen peroxide, the latter being monitored amperometrically. See, for example, U.S. Pat. Nos. 3,539,455 to Clark and 4,671,288 to Gough.
Although the idea of an implantable enzymatic glucose sensor is not per se new, considerable difficulty has been encountered in producing reliable, cost-efficient devices of this character. For example, many proposed sensor geometries are simply not realistically implantable, at least for the periods of time required for adequate clinical glucose monitoring. Thus, the devices proposed in the '288 Gough Patent, because of a requirement of multiple electrodes carried within a tubular needle, inevitably are of such diameter as to be uncomfortable to the user and not practical for extended implantation. Furthermore, many prior sensors do not exhibit a stable and linear response, particularly over extended times of implantation, and do not give accurate and reliable results. Finally, fabrication of prior glucose sensors has presented formidable difficulties, to the extent that only about one in five sensors produced by conventional techniques are deemed usable. This obviously represents a considerable inefficiency, to the point that no truly successful implantable glucose sensor has heretofore been produced on a large scale.